While the specificity and timing of membrane fusion in diverse physiological reactions, including virus-cell fusion, is determined by proteins, fusion always involves the merger of membrane lipid bilayers. We have isolated a lipid-dependent stage of cell-cell fusion mediated by influenza hemagglutinin, HA, and triggered by cell exposure to mildly acidic pH. This stage precedes actual membrane merger and fusion pore formation; but is subsequent to a low pH-induced change in HA conformation including insertion of HA fusion peptide into the target membrane. The low pH conformation of HA is required not only to achieve this lipid-dependent stage but also, downstream of it, to drive fusion to completion. The lower the pH that is applied to trigger fusion and, thus, the more HA molecules are activated, the less profound is the dependence of fusion on lipids. Membrane-incorporated lipids affect fusion in a manner that correlate with their dynamic molecular shape, a characteristic which determines a lipid monolayer's propensity to bend in different directions. To further elucidate the pathway and the mechanisms of membrane fusion in a relatively simple experimental system we also studied fusion of phospholipid vesicles to planar phospholipid bilayer membranes. Surprisingly the fusion intermediates detected in this protein-free system (hemifusion and flickering fusion pores) appear to be very similar with the known structural intermediates of biological fusion. These data, and the lipid sensitivity of HA-mediated fusion, are consistent with the stalk hypothesis of fusion suggesting that fusion proteins begin membrane merger by promoting the formation of a bent, lipid-involving, stalk-like intermediate common for biological fusion and the fusion of purely lipidic bilayers.